Coregulation of transcription factor binding and nucleosome occupancy through DNA features of mammalian enhancers.
Coregulation of transcription factor binding and nucleosome occupancy through DNA features of mammalian enhancers.
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DOI：
10.1016/j.molcel.2014.04.006
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发表时间：
2014-06-05
期刊：
影响因子：
16
通讯作者：
Natoli, Gioacchino
中科院分区：
文献类型：
--
作者：
Barozzi, Iros;Simonatto, Marta;Bonifacio, Silvia;Yang, Lin;Rohs, Remo;Ghisletti, Serena;Natoli, Gioacchino
转录因子（TF）优先结合计算预测的高核小体占有率区域中包含的位点，表明核小体是TF结合位点的守门人。然而，由于它们的复杂性，哺乳动物基因组包含数百万个随机发生的未结合的TF共有结合位点。我们假设控制核小体组装的信息可能与使TF能够结合顺式调节元件而忽略随机发生的位点的信息一致。因此，核小体将选择性地掩盖与TF接触的基因组位点，从而具有潜在的功能。造血TF Pu.1在巨噬细胞特异性增强子处维持核小体消耗，该增强子在其他细胞类型和重建的染色质中显示广泛的核小体占用。我们确定了一组最小的DNA序列和形状特征，准确预测Pu.1结合和核小体占用全基因组。这些数据揭示了哺乳动物顺式调节元件的基本组织原理，即TF募集和核小体沉积由重叠的DNA序列特征控制。
Transcription factors (TFs) preferentially bind sites contained in regions of computationally predicted high nucleosomal occupancy, suggesting that nucleosomes are gatekeepers of TF binding sites. However, because of their complexity mammalian genomes contain millions of randomly occurring, unbound TF consensus binding sites. We hypothesized that the information controlling nucleosome assembly may coincide with the information that enables TFs to bind cis-regulatory elements while ignoring randomly occurring sites. Hence, nucleosome would selectively mask genomic sites contacted by TFs and thus potentially functional. The hematopoietic TF Pu.1 maintained nucleosome depletion at macrophage-specific enhancers that displayed a broad range of nucleosome occupancy in other cell types and in reconstituted chromatin. We identified a minimal set of DNA sequence and shape features that accurately predicted both Pu.1 binding and nucleosome occupancy genome-wide. These data reveal a basic organizational principle of mammalian cis-regulatory elements whereby TF recruitment and nucleosome deposition are controlled by overlapping DNA sequence features.
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